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991.
Morgan NV Essop F Demuth I de Ravel T Jansen S Tischkowitz M Lewis CM Wainwright L Poole J Joenje H Digweed M Krause A Mathew CG 《Blood》2005,105(9):3542-3544
Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer. We report that a deletion mutation in the FANCG gene (c.637_643delTACCGCC) was present in 82% of FA patients in the black populations of Southern Africa. These patients originated from South Africa, Swaziland, Mozambique, and Malawi. The mutation was found on the same haplotype and was present in 1% of controls from the black South African population. These data indicate that the birth incidence of FA in this population is higher than 1 in 40 000, which is much higher than previously supposed, and suggest that the FANCG deletion is an ancient founder mutation in Bantu-speaking populations of sub-Saharan Africa. Diagnostic screening is now possible by means of a simple DNA test. 相似文献
992.
Ruth Chieng John Coutsouvelis Susan Poole Michael J. Dooley Diana Booth Andrew Wei 《Supportive care in cancer》2013,21(12):3491-3495
Purpose
Patients having undergone allogeneic stem cell transplantation (SCT) require complex medication regimens. To ensure the safe and effective management of this patient group, specialised care in a centre with a dedicated and experienced healthcare team is essential. The aim of this study was to evaluate the effectiveness of a specialty clinical pharmacist working in an ambulatory SCT clinic.Methods
A prospective cohort study was conducted on patients post SCT and discharged to the ambulatory setting. Patients were reviewed by a clinical pharmacist weekly for six visits. At these visits a medication review was undertaken. Interventions from these reviews were recorded. Interventions were then assigned a risk rating by a multidisciplinary panel. Adherence was also assessed by a Morisky questionnaire and review of dose administration aids. Comparison of data over the six-visit period was undertaken.Results
In total 23 patients were enrolled in the study. All six visits were completed in 17 patients and 161 interventions were recorded at an average of 1.4 interventions per patient visit. The panel rated 40 % of interventions as high risk, 46 % as medium risk and 14 % as low risk. At all visit points high- and medium-risk interventions constituted >80 % of the total. Morisky scores improved by an average of 1.53 (p?<?0.0001) between visits 1 and 6. All patients were scored as highly adherent by visit 6.Conclusions
A specialist clinical pharmacist in the SCT outpatient clinic resulted in regular and effective intervention contributing to improved medication management and adherence. 相似文献993.
Olga Konopatskaya Karen Gilio Matthew T. Harper Yan Zhao Judith M.E.M. Cosemans Zubair A. Karim Sidney W. Whiteheart Jeffery D. Molkentin Paul Verkade Steve P. Watson Johan W.M. Heemskerk Alastair W. Poole 《The Journal of clinical investigation》2009,119(2):399-407
Platelets are central players in atherothrombosis development in coronary artery disease. The PKC family provides important intracellular mechanisms for regulating platelet activity, and platelets express several members of this family, including the classical isoforms PKCα and PKCβ and novel isoforms PKCδ and PKCθ. Here, we used a genetic approach to definitively demonstrate the role played by PKCα in regulating thrombus formation and platelet function. Thrombus formation in vivo was attenuated in Prkca–/– mice, and PKCα was required for thrombus formation in vitro, although this PKC isoform did not regulate platelet adhesion to collagen. The ablation of in vitro thrombus formation in Prkca–/– platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKCα expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding, including gastrointestinal and tail bleeding, was not seen in Prkca–/– mice. In summary, the effects of PKCα ablation on thrombus formation and granule secretion may implicate PKCα as a drug target for antithrombotic therapy. 相似文献
994.
Implantable cardioverter Defibrillator (ICD) therapy has been extensively evaluated in patients at high risk of sudden cardiac
death. Most recently, the Sudden Cardiac Death in Heart Failure Trial found that patients with moderate symptoms of congestive
heart failure, whether due to an ischemic or a nonischemic cause, have reduced mortality compared with patients treated only
with conventional medical therapy for heart failure. The results of this trial confirm those of earlier trials finding a benefit
of ICD therapy in patients with coronary artery disease and reduced left ventricular systolic function, and extend the indications
for ICD therapy to those without coronary artery disease. 相似文献
995.
Aurich M Mwale F Reiner A Mollenhauer JA Anders JO Fuhrmann RA Kuettner KE Poole AR Cole AA 《Arthritis and rheumatism》2006,54(1):244-252
OBJECTIVE: Although cartilage lesions occur in the ankles, osteoarthritis rarely develops in the ankles, suggesting that ankle cartilage can up-regulate mechanisms to repair the damaged matrix. To define these processes, we compared cartilage samples obtained from normal tali and from lesional sites of damaged tali. METHODS: Cartilage samples were obtained from the tali of normal ankles and from 3 sites on tali with lesions (the lesion, adjacent to the lesion, and far removed from the lesion). Cartilage was analyzed for type II collagen (CII) messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). For the assessment of type IX collagen, the COL2 and NC4 domains were evaluated. The cartilage samples were also assayed for glycosaminoglycans, epitope 846 of aggrecan, and DNA. RESULTS: The DNA content, epitope 846, COL2(IX), and the denaturation epitope were significantly increased in lesional cartilage. Although there was a tendency toward an increase in CII content and CPII, the increase did not reach significance. Neither the NC4(IX) domain nor Col2-3/4C was elevated. Surprisingly, changes in cartilage both adjacent to and remote from the lesion were similar to those in the lesion. CONCLUSION: The changes observed in cartilage obtained from the lesion and from sites adjacent to the lesion were not surprising; however, the changes in cartilage obtained from sites remote from the lesion were unexpected. This up-regulation of matrix turnover in ankles with degenerative lesions may indicate a physiologic response of the entire articular surface to repair the damaged matrix, which is not restricted to the lesion site. This suggests that there may be some mechanism of communication across the cartilage. The response by ankle cartilage obtained from a site remote from the lesion has not been observed in the knee. 相似文献
996.
Associations between joint space narrowing and molecular markers of collagen and proteoglycan turnover in patients with knee osteoarthritis 总被引:2,自引:0,他引:2
Mazzuca SA Poole AR Brandt KD Katz BP Lane KA Lobanok T 《The Journal of rheumatology》2006,33(6):1147-1151
OBJECTIVE: We examined whether plasma concentrations of biomarkers of the collagenase cleavage of type II collagen (C2C), types I and II collagens (C1,2C), type II collagen synthesis (CPII), proteoglycan aggrecan turnover (CS846), and the ratio C2C:CPII would distinguish subjects with progressive radiographic osteoarthritis (OA) from those with stable disease. METHODS: Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month clinical trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months, and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Plasma samples were obtained every 6 months for determination of C2C, CPII, CS846, and C1,2C. RESULTS: None of the biomarkers was a significant predictor of progression of JSN. Over the interval from baseline to 16 months, the mean and the maximum of the intercurrent CS846 values were significantly associated with JSN (i.e., 0.12-0.14 mm of JSN per SD decrease in mean or maximum CS846; p < 0.01). The mean of serial CS846 levels was related to JSN also during the interval between months 16 and 30. CONCLUSION: Markers of type II collagen synthesis/degradation and of proteoglycan aggrecan turnover were not predictive of JSN in knee OA in this pilot study. However, serial concentrations of proteoglycan aggrecan epitope CS846 were associated with JSN during both the intervals studied. 相似文献
997.
Harry C. Alexander Adam S. Bartlett Cameron I. Wells Jacqueline A. Hannam Matthew R. Moore Garth H. Poole Alan F. Merry 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2018,20(9):786-794
Background
Consistent measurement and reporting of outcomes, including adequately defined complications, is important for the evaluation of surgical care and the appraisal of new surgical techniques. The range of complications reported after LC has not been evaluated. This study aimed to identify the range of complications currently reported for laparoscopic cholecystectomy (LC), and the adequacy of their definitions.Methods
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for prospective studies reporting clinical outcomes of LC, between 2013 and 2016.Results
In total 233 studies were included, reporting 967 complications, of which 204 (21%) were defined. One hundred and twenty-two studies (52%) did not provide definitions for any of the complications reported. Conversion to open cholecystectomy was the most commonly reported complication, reported in 135 (58%) studies, followed by bile leak in 89 (38%) and bile duct injury in 75 (32%). Mortality was reported in 89 studies (38%).Conclusion
Considerable variation was identified between studies in the choice of measures used to evaluate the complications of LC, and in their definitions. A standardised set of core outcomes of LC should be developed for use in clinical trials and in evaluating the performance of surgical units. 相似文献998.
Ellen L. Poole MS RN CPAN CCRN Assistant Professor of Nursing 《Journal of PeriAnesthesia Nursing》1996,11(6):402-403
The American Society of PeriAnesthesia Nurses has long held the standard that two licensed personnel will be in the PACU during phase I of recovery. Not all areas of the country have been able to adhere to this standard. This is one nurse's reflections on the time spent “working alone” in the PACU. This article was written before the November 1995 ASPAN position paper on staffing issues. The author strongly feels that with the position paper in place, facilities will make a stronger effort to adhere to the standard and working alone will become a matter of historical record. 相似文献
999.
The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. 总被引:21,自引:1,他引:21 下载免费PDF全文
J Antoniou T Steffen F Nelson N Winterbottom A P Hollander R A Poole M Aebi M Alini 《The Journal of clinical investigation》1996,98(4):996-1003
Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration. 相似文献
1000.